This article focuses on neuropsychological functioning at moderate, high, and extreme altitude. This article summarizes the available literature on respiratory, circulatory, and brain determinants on adaptation to hypoxia that are hypothesized to be responsible for neuropsychological impairment due to altitude. Effects on sleep are also described. At central level, periventricular focal damages (leuko-araiosis) and cortical atrophy have been observed. Frontal lobe and middle temporal lobe alterations are also presumed. A review is provided regarding the effects on psychomotor performance, perception, learning, memory, language, cognitive flexibility, and metamemory. Increase of reaction time and latency of P300 are observed. Reduced thresholds of tact, smell, pain, and taste, together with somesthetic illusions and visual hallucinations have been reported. Impairment in codification and short-term memory are especially noticeable above 6,000 m. Alterations in accuracy and motor speed are identified at lower altitudes. Deficits in verbal fluency, language production, cognitive fluency, and metamemory are also detected. The moderating effects of personality variables over the above-mentioned processes are discussed. Finally, methodological flaws found in the literature are detailed and some applied proposals are suggested.

IntroductionWe report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD.MethodsThis was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy. Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa. The primary end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of − 50 mL in the per-protocol (PP) population. The incidence of adverse events was also assessed.ResultsIn total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population. UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28–77 mL); p < 0.001]. Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV1 at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34–3.14). Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.ConclusionIn this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD. Both treatments had similar safety profiles. These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.Trial RegistrationClinicalTrials.gov identifier NCT02799784.FundingGlaxoSmithKline.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0626-4) contains supplementary material, which is available to authorized users.

BackgroundIt has recently been proposed that the concept of clinical control in COPD may be useful for deciding treatment in COPD, but the original control criteria (OCC) were considered too restrictive.ObjectiveDefine and subsequently validate “modified” control criteria (MCC) of COPD.MethodProspective observational study in COPD patients with a 1-year follow-up. Control was defined as the presence of low clinical impact and clinical stability. To evaluate clinical impact, the following clinical parameters were assessed: the degree of dyspnea, use of rescue medication, physical activity, and sputum color. Stability was assessed by clinical changes and exacerbations in the last 3 months. The COPD assessment test score and their changes were also evaluated as alternative control criteria. To define the MCC, adjustment for disease severity using BODEx index (MCC-B) or FEV1 (MCC-F) was evaluated, and the best cutoff point was established. Time to first combined event (emergency visit, hospitalization, or death) was analyzed to evaluate the predictive capacity of risk of the OCC, MCC-B, and MCC-F.ResultsWe included 265 patients, 224 (83.9%) men, with a mean age (±SD) of 68±9 years and FEV1 of 58%±17%. The proportion of controlled patients was higher using clinical MCC-B or MCC-F (61.5% and 59.6%) than OCC (27.5%). Similar percentages were found using COPD assessment test scores. The time to the first combined event was significantly greater in controlled patients using MCC criteria (P<0.001, all cases). The predictive capacity of risk was similar in MCC-B (c-statistic [C]=0.639) and MCC-F (C=0.637) and higher than OCC (C=0.589).ConclusionsThe new MCC identified a higher number of controlled COPD patients. These patients have a better quality of life and lower risk of poor outcomes. The concept of control and the new MCC could be a useful tool to optimize therapy.

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